Sudden cardiac death (SCD) is one of the leading causes of mortality in the general population, accounting for 5-15% of total deaths in the United States and other industrialized countries.1,2 With the advent of antiretroviral therapy, HIV-infected individuals now are faced with health issues related to aging, including cardiovascular disease. Individuals with HIV have higher rates of coronary events compared to controls and a growing body of literature from our group and others demonstrates that they are at increased risk for developing accelerated atherosclerosis.3,4 Emerging studies suggest that HIV-related inflammation is independently associated with premature coronary artery disease.5,6 In addition, other cardiovascular abnormalities have been described in the setting of HIV infection including cardiomyopathy,7 pulmonary hypertension8 and a prolonged QT interval,9,10 all of which make SCD an important health concern in this patient population. Our group has recently shown that SCD accounts for the largest proportion of non-AIDS deaths among HIV-infected individuals, at a rate that is over four-fold higher than the background population. While the exact mechanisms behind SCD in this population are unknown, malignant arrhythmias likely play a strong role. Prior myocardial infarction and structural heart disease are major risk factors for malignant arrhythmias in the general population, but the rates and risk factors for ventricular arrhythmias and SCD in the setting of HIV infection are unknown. HIV-specific factors such as chronic inflammation,19 antiretroviral use,4, 9 or direct viral effect on cardiomyocyte repolarization 22, 3 may interact with the arrhythmogenic substrate of cardiovascular disease (CVD) to substantially increase the risk of arrhythmia. We hypothesize that HIV-infected patients with CVD will have higher rates of ventricular arrhythmias compared to matched HIV-negative controls with similar heart disease. To address this hypothesis, we will evaluate pathologic electrocardiographic (ECG) parameters and ventricular arrhythmias in cardiac patients with and without HIV using 48-hour ambulatory Holter monitoring and 12-lead ECGs. Additionally, we will evaluate the association of inflammatory markers and HIV-related factors with SCD in a large outpatient cohort of HIV-infected individuals. This study will form the basis for future investigations that wll assess whether certain interventions, either HIV-related or cardiovascular, are successful in reduction of SCD in the setting of HIV infection.